How Do NSAIDs Work on a Molecular Level?
The main mechanism of action of NSAIDs is the inhibition of COX enzymes (more specifically, the inhibition of the COX activity of prostaglandin H synthase enzymes) (see Figure 1) (Ulrich et al., 2006; Gupta and DuBois, 2001). Two closely related forms of COX exist: COX-1, which is expressed on a constitutive basis in many tissues, and COX-2, which can be induced and plays a role in many inflammatory and proliferative processes. Both COX enzymes synthesize prostaglandin H, a precursor of several prostaglandins and other eicosanoids that are produced by multiple specific synthases. The COX-enzymes are the bottleneck in this process. Prostaglandin E2 appears to be most relevant for carcinogenesis; this signalling molecule has been shown to cause tumors in mouse models of colon carcinogenesis and is connected to several other signalling pathways that are relevant to cancer formation. Cancer cells appear to utilize several mechanisms to increase the amount of pro-carcinogenic prostaglandins
